Field of the Invention
The present invention relates generally to the preparation of topical and oral compositions. More particularly, it relates to the preparation of ionic polymer delivery systems which prolong the activity of various topically active ingredients by increasing the substantivity on keratinic materials, such as hair and skin, and to orally delivered polymers which release active substances via ion-exchange.
The adherent properties of topically-applied substances on hair and skin affects both initial adsorption and retention, particularly on subsequent exposure to water. The combined characteristics of adsorption and retention constitute the property referred to as "substantivity," which can be defined as the ability of a substance to be adsorbed onto keratin and to resist removal by water rinse-off.
An ideal topical substance would have adsorptive affinity for keratinic materials, retain activity for long periods of time, resist being washed away by perspiration and other contact with water, and be free of adverse interactions with other ingredients of which incorporation is desirous. No topical substance has yet been discovered which adequately satisfies all of these objectives.
Some of the most popular topically active preparations available in the market today include, for example, fragrance substances; cosmetic substances, such as lipsticks, make-up and foundation powders; insect repellents; anti-bacterials; acne treatment formulations; hair treatment formulations, such as conditioners and hair growth promoting agents; and skin protection formulations, such as age-prevention agents; and ultraviolet absorbing substances (sunscreens). These ingredients, substances, or formulations may be used alone, or in combination with each other, and may be applied in pure form or diluted in a suitable solvent or carrier.
A frequently observed problem with such topically active substances is the rapid loss of activity after application to the skin. Under usual conditions of heavy perspiration and/or contact with water, concentration of the above substances in their respective topical compositions is either diluted, thereby reducing effectiveness, or washed away, thereby losing all effectiveness. One way to extend activity is by increasing the concentrations of the active ingredient in their respective formulations. However, as concentrations are increased, so too are the risks of toxic and allergic reactions to the user. These reactions often occur with the higher concentrations, even if exposure to the product is relatively short.
A second drawback, unrelated to the safety of administration of such compositions, is the increased expense of using such compositions which are so easily washed away. For instance, to maintain an adequate level of protection from the sun, a sunbather would have to reapply sunscreen each time after entering the water and frequently after perspiring.
It would therefore be highly desirable to provide an approach for increasing the adsorptive affinity of topically active compositions to keratinic materials, and for prolonging the activity of such compositions, while simultaneously reducing the likelihood of toxic and/or allergic reaction to the user.
Compositions and methods for the release of an active substance, such as a drug, from a reservoir over time are known, and numerous specific approaches exist to achieve such controlled release. Two widely practiced approaches are of particular interest to the present invention. In the first such approach, drugs or other active substances are encapsulated or coated with a material which dissolves or degrades in response to a change in environmental conditions. For example, pH-response coatings (referred to as enteric coatings) may be provided on drugs to protect the drug in the low pH environment of the stomach but dissolve when the pH rises as the drug passes to the intestines. Such coatings include cellulose acetate, phthalate-polyvinyl acetate phthalate, hydroxypropylcellulose phthalate, methyl cellulose phthalate, and the like. Although these coatings are very effective in protecting drugs in the stomach, they do not generally provide a controlled release rate once the drug reaches the intestines.
A less widely employed delivery approach utilizes porous polymeric particles for absorbing and releasing drugs and other active substances at a controlled release rate. See, e.g., U.S. Pat. No. 4,692,462, discussed below. In such systems, the diffusion rate of the drug or other active substance through the pores determines the release rate. The diffusion rate, of course, depends on pore size, drug viscosity, temperature, and the like. In the case of drug delivery, drugs absorbed in porous polymeric particles are usually combined in an adhesive or other matrix material as part of a transdermal drug delivery system. In another example, drugs have been adsorbed onto porous resin beads which are then coated with a membrane diffusion barrier, e.g., ethylcellulose, in order to effect sustained release. See, European Patent Application 171 528, discussed below.
One difficulty with these systems is that a coating or blocking agent must be introduced in order to achieve a desired release rate for particular active substances. The physical characteristics of drugs and other active substances may vary widely, including changes in viscosity, charge characteristics, molecular weight, and the like and the release rate in any delivery system may vary widely depending on the nature of the substance which is being delivered. This problem is particularly evident when employing porous particle delivery systems where modification of the pore characteristics can be achieved only within certain limitations. Synthetic resin-based ion exchangers are conventionally produced by post-polymerization modification of preformed, cross-linked beads. For example, anion exchange resins are made from cross-linked polystyrene by halogen-alkylation and subsequent amination. Cation exchange resins can be made by either carboxylation or sulfonylation of the preformed, cross-linked beads. Such ion exchange resins are typically discolored, have capacities for the exchange of ion less than 2 meq/gm, and regeneration can be a lengthy process. Naturally occurring ion exchangers, such as cellulose-based or dextran gels which are made by introducing functional groups onto the cross-linked natural polymers, have gel structures which are not mechanically strong enough to prevent the gel matrix from shrinking or collapsing as the active ingredient is removed. The natural polymer-based materials are unstable in the presence of oxidants or strong acids, at elevated temperatures (e.g., 120.degree. C. for 30 minutes), and because of their biological origins, they will support bacterial and microbial growth.
Thus, it would be desirable to provide improved compositions and methods for the delivery of drugs and other active substances. It would be particularly desirable if the compositions could be readily modified to achieve a desired release rate for active substances having a wide range of physical and chemical characteristics. It would be further desirable if the compositions could be modified to control the release rate of such diverse active substances under a variety of different external conditions, such as pH, temperature, ionic strength, and the like. It would also be desirable if compositions could be readily modified to allow absorption of bile salts in a controlled and predictable manner.